#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Molecular autopsy and sudden cardiac death in the young


Authors: Rücklová Kristina 1;  Kulvajtová Markéta 2;  Krebsová Alice 3;  Dobiáš Martin 4;  Petřková Jana 5
Authors‘ workplace: Klinika dětí a dorostu FNKV a Klinika dětského a dorostového lékařství VFN, Praha 1;  Ústav soudního lékařství 3. LF UK a FNKV, Praha 2;  Centrum dědičných kardiovaskulárních onemocnění, IKEM, Praha 3;  Ústav soudního lékařství a medicínského práva FNOL a LF UP, Olomouc 4;  I. Interní klinika-kardiologická FNOL a LF UP, Laboratoř kardiogenomiky FNOL, Ústav lékařské genetiky FNOL a LF UP, Olomouc 5
Published in: Soud Lék., 65, 2020, No. 1, p. 2-6
Category: Review

Overview

Sudden cardiac death is defined as sudden death due to a confirmed cardiovascular disease or when there is no explanation after medico-legal autopsy and arrhythmogenic, possibly hereditary etiology is presumed. Molecular autopsy should be indicated in all cases of sudden cardiac death due to suspected cardiomyopathy and hereditary arrhythmic syndrome. It should also be considered in thoracic aortic dissection. These hereditary cardiovascular diseases account for the majority of sudden cardiac death cases in the young up to 40 years of age. They are mostly inherited in an autosomal dominant manner carrying a 50% risk of passing the diasease-causing mutation to the offspring. In fact, all first-degree relatives have a high risk of developing the disease associated with sudden cardiac death. Hence, knowledge of the exact cause of death derived from molecular autopsy combined with a cardiologic and targeted genetic examination of first-degree relatives may help us detect other at risk family members and provides us with an opportunity to prevent further sudden deaths in the family by means of timely preventive measures. Forensic pathologists play a key role in this process of primary prevention of sudden death. They should retain tissue samples for DNA analysis whenever a hereditary cardiovascular disease is suspected. They should also recommend to the relatives a thorough cardiogenetic examination at one of the specialized centres. A multipdisciplinary team including cardiologists, geneticists, psychologists, forensic pathologists and coroners should be involved in the investigation of sudden cardiac death in the young.

Keywords:

cardiomyopathy – molecular autopsy – hereditary arrhythmic syndromes – hereditary thoracic aortic aneurysms and dissections


Sources

1.    Priori SG, Blomstrom-Lundqvist C, Mazzanti A, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC) endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015; 36 (41): 2793-2867.

2.    Ripperger T, Tröger HD, Schmidtke J. The genetic message of a sudden, unexpected death due to thoracic aortic dissection. Forensic Sci Int 2009; 187: 1-5.

3.    Gago-Díaz M, Ramos-Luis E, Zoppis S, et al. Postmortem genetic testing should be recommended in sudden cardiac death cases due to thoracic aortic dissection. Int J Legal Med 2017; 131: 1211-1219.

4.    Winkel BG, Holst AG, Theilade J, et al. Nationwide study of sudden cardiac death in persons aged 1-35 years. Eur Heart J 2011; 32: 983-990.

5.    Semsarian C, Hamilton RM. Key role of the molecular autopsy in sudden unexpected death. Heart Rhythm 2012; 9: 145-150.

6.    Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis and therapy. Circ Res 2017; 121: 749-770.

7.    Corrado D, Basso C, Judge DP. Arrhythmogenic cardiomyopathy. Circ Res 2017; 121: 784-802.

8.    McNally EM, Mestroni L. Dilated cardiomyopathy: genetic determinants and mechanisms. Circ Res 2017; 121: 731-748.

9.    Pinard A, Jones GT, Milewicz DM. Genetics of thoracic and abdominal aortic diseases: aneurysms, dissections, and ruptures. Circ res. 2019; 124: 588-606.

10.  Verhagen JMA, Kempers M, Cozijnsen L, Bouma BJ, Duijnhouwer AL, Post JG, et al. Expert consensus recommendations on the cardiogenetic care for patients with thoracic aortic disease and their first-degree relatives. Int J Cardiol 2018; 258: 243-248.

11.  Bagnall RD, Weintraub RG, Ingles J, et al. A prospective study of sudden cardiac death among children and young adults. N Engl J Med 2016; 374: 2441-2452.

12.  Lahrouchi N, Raju H, Lodder EM, et al. Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome. JACC 2017; 69 (17): 2134-2145.

13.  Marcondes L, Crawford J, Earle N, et al. Long QT molecular autopsy in sudden unexplained death in the young (1-40 years old): lessons learnt from na eight year experience in New Zealand. PLOS ONE 2018; 1-17.

14.  Tester DJ, Medeiros-Domingo A, Will ML, Haglund CM, Ackerman MJ. Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy-negative sudden unexplained death referred for postmortem genetic testing. Mayo Clin Proc 2012; 87(6): 524-539.

15.  Basso C, Aguilera B, Banner J, et al. Guidelines for autopsy investigation of sudden cardac death: 2017 update from the Association for European Cardiovascular Pathology. Virchows Arch 2017; 471: 691-705.

16.  Skinner JR, Winbo A, Abrams D, Vohra J, Wilde AA. Channelopathies that lead to sudden cardiac death: clinical and genetic aspects. Heart, Lung and Circulation 2019; 28: 22-30.

17.  Post-mortem in sudden unexpected death in the young: Guidelines on autopsy practice. Prepared by the members of Trans-Tasman Response AGAinst sudden Death in the Young (TRAGADY). Endorsed by the Royal College of Pathologists of Australasia. Officially endorsed by the National Heart Foundation of New Zealand.

18.  Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The task force for the diagnosis and treatment of aortic diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014; 35 (41): 2873-2926.

19.  Pinard A, Salgado D, Desvignes JP, Rai G, Hanna N, Arnaud P, et al. WES/WGS Reporting of Mutations from Cardiovascular „Actionable“ Genes in Clinical Practice: A Key Role for UMD Knowledgebases in the Era of Big Databases. Hum Mutat 2016; 37(12): 1308-1317.

20.  Sepši M, Zeman M, Synková I, et al. Náhlá srdeční smrt a její diagnostika. Kardiol Rev Int Med 2017; 19(4): 247-250.

21.             Zeman M, Sepši M, Vojtíšek T, Šindler M. Suddenly deceased young individuals autopsied at the Department of forensic medicine, Brno - analysis. Soud

Labels
Anatomical pathology Forensic medical examiner Toxicology
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#